The first radionuclide to be widely used for bone scanning was Sr-85. Strontium-85 is rapidly accumulated by bone after intravenous administration and images of the skeletal system are possible. However, Sr-85 has a long physical half life (65 days) and a long biological half life (.about.800 days) which limits the levels which can be administered. Also, the high energy of the gamma photon emitted (514 key) is difficult to collimate.
Fluorine-18 has also been used to image the skeletal system. It is a positron emitter with a half life of 1.85 hr. Although F-18 has good physical properties for imaging, it has some serious drawbacks. Fluorine-18 is cyclotron produced and, therefore, expensive. Also its distribution is limited due to its short half life.
Many organ scanning agents, including those for the skeletal system, have now been replaced with complexes of Technetium-99 m. This nuclide has ideal physical properties (T.sub.1/2 =6 hr., gamma photon of 141 kev) for imaging. In addition, it is readily available because of the Mo-99/Tc-99 m generators. Thus, the majority of imaging is now done using Tc-99 m.
Technetium-99 m is obtained from generators in the +7 oxidation state as the pertechnetate ion (TcO.sub.4.sup.-). In order to form a complex, Tc must be in a lower oxidation state, i.e. +3, +4 or +5. Although other reducing agents can be used, Sn.sup.2+ has been employed most often. Thus Tc-99 m complexes can be formed by reduction of TcO.sub.4.sup.- using Sn.sup.2+ in the presence of a complexing agent. This is usually done in an aqueous saline solution that is suitable for intravenous injection.
Commercial complexing agents are sold as "radiopharmaceutical kits". A "kit" consists of an evacuated vial containing the complexing agent, a reducing agent, and possibly a buffer and stabilizers. To prepare the Tc-99 m complexes, a few milliliters of sodium pertechnetate solution in saline is injected into the vial. An adequate amount of the resultant solution is used for imaging.
Subramanian et al (Radiology, Vol. 99, pp. 199-196, 1971) reported the use of a complex of Tc-99 m and an inorganic polyphosphate for skeletal imaging. Several others have reported inorganic polyphosphates as useful for this purpose (see U.S. Pat. Nos. 3,852,414; 4,016,249; and 4,082,840). The use of pyrophosphate (PYP) for bone imaging has also been taught (U.S. Pat. Nos. 3,851,044; 3,931,396; and 4,075,314). The Tc-phosphates had fair success but have been replaced by Tc-phosphonates.
Complexes of Tc-99 m with phosphonic acids show higher bone uptake with faster blood clearance than Tc-99 m/phosphate complexes. Phosphonic acids which are considered the best bone scanning agents when complexed with Tc-99 m include hydroxyethanediphosphosphonate (EHDP), methylenediphosphonate (MDP) and hydroxymethylenediphosphonate (see U.S. Pat. Nos. 3,983,227; 3,989,730; 4,032,625 and also J. Nucl. Med. 21, pg. 767; Radiology 136, pg. 209; J. Nucl. Med. 21, pg. 961; Radiology 136, pg. 747).
Evaluation of skeletal imaging agents has been, for the most part, limited to comparing total bone uptake to the rate of blood clearance through the kidneys in order to arrive at the best contrast between bone and soft tissue. However, it has been suggested that better lesion detection may be possible if the scanning agents have a high uptake in fast growing bone as compared with normal bone (see Clinical Nuclear Medicine, Vol. 7, pg. 403). Therefore a need exists for a Tc-99 m complex with high ratios of fast growing bone/normal bone uptake.
Another application for agents that have high ratios of fast growing bone to normal bone uptake is as a therapeutic agent. It may be possible to treat bone metastasis with a beta emitting radionuclide if it can be concentrated in the area of the metastasis. Therefore, if a beta-emitting agent that had a high uptake in fast growing bone and relatively low uptake in normal bone was found, it could prove to be an effective therapeutic agent.
Several nuclides may be of therapeutic utility. For example Re-186 has a half life of 90.6 hr. and beta-radiation of 1.076 and 0.939 MeV. Also, since the chemistry of Re is very similar to that of Tc, it is probable that the biolocalization of Re-complexes would be similar to that of Tc-complexes. There are other nuclides, especially of the lanthanide group of metals, that may also be therapeutically useful.